The Effect of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Hereditary Spastic Paraplegia

Abstract

Background. Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited disorders affecting predominantly the motor cortex and pyramidal tract, which results in slowly progressing gait disorders, as well as spasticity and weakness of lower extremities. Repetitive transcranial magnetic stimulation (rTMS) has been previously investigated as a therapeutic tool for similar motor deficits in a number of neurologic conditions. The aim of this randomized, controlled trial was to investigate the therapeutic potential of rTMS in various forms of HSP, including pure and complicated forms, as well as adrenomyeloneuropathy. Methods. We recruited 15 patients (five women and 10 men; mean age 43.7±10.6 years) with the mentioned forms of HSP. The intervention included five sessions of bilateral 10 Hz rTMS over primary motor areas of the muscles of lower extremities and five sessions of similar sham stimulation. Results. One patient dropped out due to seizure, and 14 patients completed the study protocol. After real stimulation, the strength of the proximal and distal muscles of lower extremities increased, and the spasticity of the proximal muscles decreased. Change in spasticity was still present during follow-up assessment. No effect was observed regarding gait velocity. No changes were seen after sham stimulation. A post hoc analysis revealed an inverse relation between motor threshold and the change of the strength after active rTMS. Conclusions. rTMS may have potential in improving weakness and spasticity of lower extremities in HSP, especially of proximal muscles whose motor areas are located more superficially. This trial is registered with Clinicaltrials.gov NCT03627416.

A Randomized Controlled Trial of the Effect of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex on Lower Extremity Spasticity in Hereditary Spastic Paraplegia

“…Despite differences between our study design and this study, they both conclude that rTMS has a palliative effect on lower limb spasticity. 13 Given the scarcity of the literature on the use of rTMS in HSP, we review some studies that used rTMS in conditions with similarity to HSP in regards to the pathophysiologic pathways involved. Table 3 highlights the studies that we review here.…”

“…Despite differences between our study design and this study, they both conclude that rTMS has a palliative effect on lower limb spasticity. 13…”

“…This study found rTMS effective in reducing the spasticity in these patients. 13 Given the effect of rTMS in the motor cortex's neural plasticity and the vast literature on its use in alleviating spasticity, we aimed to study its effectiveness as a palliative measure for lower limb spasticity, function, and gait improvement in patients with HSP.…”

Recent advances in understanding hereditary spastic paraplegias and emerging therapies

“…Several other symptomatic treatments have been tested and described through case reports or a cohort with very few patients. The treatments tested are, for instance, transcranial magnetic stimulation 71 , spinal cord stimulation 72 , and specific rehabilitation protocol 73 .…”

Randomized Trial of Botulinum Toxin Type A in Hereditary Spastic Paraplegia — The SPASTOX Trial

“…[14][15][16] Oral antispastic agents are frequently employed to treat spasticity in clinical practice. 14 When the response is inadequate or there are systemic side effects (such as dizziness and drowsiness), 17 which may cause falls and accidents, topic antispastic drug, 18 intrathecal baclofen application, 19 transcranial magnetic stimulation, 20 and botulinum toxin type A (BoNT-A) may be considered. BoNT-A is a first-line treatment approved for several disorders characterized by excessive muscle contraction, such as cervical dystonia, blepharospasm, and spastic arm following stroke.…”